Department of Cell and Molecular Biology, Karolinska Institutet, Berzelius väg 35, 171 77 Stockholm, Sweden.
Exp Cell Res. 2010 Jan 15;316(2):158-71. doi: 10.1016/j.yexcr.2009.08.007. Epub 2009 Aug 15.
HORMA domain-containing proteins regulate interactions between homologous chromosomes (homologs) during meiosis in a wide range of eukaryotes. We have identified a mouse HORMA domain-containing protein, HORMAD1, and biochemically and cytologically shown it to be associated with the meiotic chromosome axis. HORMAD1 first accumulates on the chromosomes during the leptotene to zygotene stages of meiotic prophase I. As germ cells progress into the pachytene stage, HORMAD1 disappears from the synapsed chromosomal regions. However, once the chromosomes desynapse during the diplotene stage, HORMAD1 again accumulates on the chromosome axis of the desynapsed homologs. HORMAD1 thus preferentially localizes to unsynapsed or desynapsed chromosomal regions during the prophase I stage of meiosis. Analysis of mutant strains lacking different components of the synaptonemal complex (SC) revealed that establishment of the SC is required for the displacement of HORMAD1 from the chromosome axis. Our results therefore strongly suggest that also mammalian cells use a HORMA domain-containing protein as part of a surveillance system that monitors synapsis or other interactions between homologs.
HORMA 结构域蛋白在多种真核生物中调节减数分裂过程中同源染色体（homologs）之间的相互作用。我们已经鉴定出一种小鼠 HORMA 结构域蛋白 HORMAD1，并从生化和细胞学角度证明其与减数分裂染色体轴相关联。HORMAD1 首先在减数分裂前期的细线期到偶线期积累在染色体上。随着生殖细胞进入粗线期，HORMAD1 从联会的染色体区域消失。然而，一旦染色体在双线期解联会，HORMAD1 再次在解联会的同源染色体轴上积累。因此，HORMAD1 在减数分裂前期优先定位于未联会或解联会的染色体区域。对缺乏联会复合体（SC）不同成分的突变株的分析表明，SC 的建立对于 HORMAD1 从染色体轴上的位移是必需的。因此，我们的结果强烈表明，哺乳动物细胞也使用 HORMA 结构域蛋白作为监测系统的一部分，该系统监测同源物之间的联会或其他相互作用。
